Retention of anergy and inhibition of antibody responses during acute γ herpesvirus 68 infection.
Retention of anergy and inhibition of antibody responses during acute γ herpesvirus 68 infection.
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DOI：
10.4049/jimmunol.1201407
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发表时间：
2012-09-15
期刊：
影响因子：
--
通讯作者：
Cambier JC
中科院分区：
文献类型：
--
作者：
Getahun A;Smith MJ;Kogut I;van Dyk LF;Cambier JC
大多数人在生命早期感染了γ疱疹病毒爱泼斯坦巴尔病毒（EBV）。一些研究结果表明，在狼疮中发现的EBV感染和致病性抗体的出现之间存在关联。γ疱疹病毒68感染成年小鼠（EBV模型）已被证明可诱导多克隆B细胞活化和高γ球蛋白血症，并增加自身抗体的产生。在这里，我们探讨了这种耐受性的破坏反映了B细胞能量损失的可能性。我们的研究结果表明，尽管无能B细胞在感染早期短暂地获得活化表型，但它们不会对自身抗原产生反应，这是通过抗原受体交联后动员Ca2+或免疫后产生抗体反应的能力来衡量的。事实上，naïve B细胞在急性感染期间也获得活化表型，但不能对t依赖性或t非依赖性抗原产生抗体反应。在急性感染动物中，抗原刺激导致共刺激分子上调，抗原特异性B细胞重新定位到B- t细胞边界，然而，这些细胞不增殖或分化为抗体分泌细胞。过继性转移实验表明，这种抑制状态是可逆的，受感染宿主体内环境的支配。最后，在缺乏CD4+ T细胞的感染小鼠中，B细胞不受抑制，这表明CD4+ T细胞在加强无反应性方面发挥了作用。因此，γ疱疹病毒68感染不是促进耐受性丧失，而是诱导免疫抑制状态，使人想起代偿性抗炎反应综合征（CARS）。
The majority of the human population becomes infected early in life by the gammaherpesvirus Epstein Barr Virus (EBV). Some findings suggest that there is an association between EBV infection and the appearance of pathogenic antibodies found in Lupus. Gammaherpesvirus 68 infection of adult mice (an EBV model) has been shown to induce polyclonal B cell activation and hypergammaglobulinemia, as well as increased production of autoantibodies. Here we explored the possibility that this breach of tolerance reflects loss of B cell anergy. Our findings show that although anergic B cells transiently acquire an activated phenotype early during infection, they do not become responsive to autoantigen as measured by the ability to mobilize Ca2+ following antigen receptor crosslinking or mount antibody responses following immunization. Indeed, naïve B cells also acquire an activated phenotype during acute infection, but are unable to mount antibody responses to either T-dependent or T-independent antigens. In acutely infected animals, antigen stimulation leads to upregulation of costimulatory molecules and relocalization of antigen-specific B cells to the B-T cell border, however, these cells do not proliferate or differentiate into antibody secreting cells. Adoptive transfer experiments show that the suppressed state is reversible and is dictated by the environment in the infected host. Finally, B cells in infected mice deficient of CD4+ T cells are not suppressed, suggesting a role for CD4+ T cells in enforcing unresponsiveness. Thus rather than promoting loss of tolerance, gammaherpesvirus 68 infection induces an immunosuppressed state, reminiscent of Compensatory Anti-inflammatory Response Syndrome (CARS).
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DOI：
10.4049/jimmunol.0803052
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Blair PA;Chavez-Rueda KA;Evans JG;Shlomchik MJ;Eddaoudi A;Isenberg DA;Ehrenstein MR;Mauri C
通讯作者：
Mauri C
影响因子：
15.3
作者：
Flaño, E;Kim, IJ;Blackman, MA
通讯作者：
Blackman, MA
B细胞通过巨细胞病毒激活。
影响因子：
15.3
作者：
Hutt-Fletcher, L M;Balachandran, N;Elkins, M H
通讯作者：
Elkins, M H
影响因子：
4.4
作者：
Guggemoos, Simone;Hangel, Doris;Adler, Heiko
通讯作者：
Adler, Heiko
影响因子：
5.4
作者：
Clambey, ET;Virgin, HW;Speck, SH
通讯作者：
Speck, SH